Multiple myeloma disease. Stages of myeloma. Mature exact symptoms of myeloma

Myeloma is a blood cancer in which malignant cells infiltrate the bone marrow and cause bone tissue damage. There are 3 stages of myeloma, each with its own clinical picture, danger and therapy. You will learn about the features of each in more detail in this article.

Characteristics of stage 1 myeloma

The first stage is characterized by a small number of malignant cells. This period is usually asymptomatic for the patient. Often the patient has no clinical signs or changes in condition, but general blood tests can accidentally detect an increase in ESR.

Hemoglobin level ≥ 100 g/l.
Calcium levels are within normal limits.
Low levels of paraproteins.

The focus of tumor growth is observed in only one bone.

At the initial stage, the disease cannot be completely cured, so therapy should be aimed at slowing the development of the disease, long-term remission, reducing symptoms and the number of malignant cells. If the disease is sluggish, then at the initial stage aggressive treatment in the form of chemotherapy or radiation therapy is not required, only constant medical supervision and supportive therapy (subcutaneous administration of interferon), which is aimed at normalizing the patient’s condition and restoring hematopoiesis.

If the disease is active, then immediate medical intervention is required.

Characteristics of stage 2

This stage is called the “high period.” At this stage, the disease begins to progress and damage bone tissue. Gradually, bone cells begin to break down, which leads to their weakening. This is one of the main manifestations of the disease, which is accompanied by a feeling of pain in the spine and ribs. The pain is not constant at first and periodically subsides; it is practically not eliminated with the help of analgesics.

When the disease activity begins to increase, the pain becomes unbearable and often occurs during movement. In addition to pain, weakness, weight loss, anemia, and tingling in the limbs appear.

Indicators:

Hemoglobin 85-100 g/l.
Calcium levels are elevated.
There is bone destruction. The affected area is most often observed in the thoracic, pelvic, spinal regions, and limbs.

Grade 2 myeloma is a rare occurrence. It is diagnosed when laboratory values are higher than in stage 1, but lower than in stage 3. This stage is dangerous for the patient because the bone fragility increases (which leads to frequent fractures), susceptibility to infections, kidney failure occurs, retinopathy and visual impairment appear.

To put the disease into remission, doctors prescribe chemotherapy, radiation therapy, and symptomatic treatment to the patient. The latter includes surgery for compression of organs, painkillers, treatment of kidney failure, etc.

Chemotherapy is given with several or one medicine. The essence of treatment is to disrupt the division of cancer cells using pharmacological agents. Once in the blood, chemotherapy drugs begin their effect throughout the body. They destroy the tumor and prevent its growth.

Radiation therapy is used if chemotherapy is ineffective. During treatment, patients may experience various adverse reactions: nausea, weakness, confusion, vomiting, etc. In this case, drugs are prescribed that mitigate the effects of side effects. Adverse reactions occur depending on the dosage and the medicine itself.

Characteristics of stage 3

This stage is called terminal. The number of pathogenic cells reaches a large number, and significant areas of bone damage appear. Infections occur, bone marrow structures are suppressed, and the body is extremely exhausted.

Indicators:

Hemoglobin level ≤ 85.
High calcium levels ≥ 2.75 mmol/l.
Protein in urine ≥ 112 g.
Multiple bone lesions are evident. Tumor sites are located simultaneously in 3 or more bones.

Gradually, the patient's height decreases, this is due to subsidence of the vertebrae and compression of the spinal cord. The x-ray shows massive signs of osteodestruction and osteoporosis. Destructive processes in the bones are usually expressed to such an extent that malignant proliferations can be palpated (especially in the chest, collarbone, and skull).

At this stage, he often gets fractures, because... normal bone structure is disrupted. You don't need to put in a lot of effort, just get a bruise.

In addition to the symptoms characteristic of stage 2, the patient experiences thrombocytopenia (decreased platelets, increased bleeding), pancytopenia (deficiency of all types of cells), depletion of the immune system, renal failure (found in 50% of patients), paraamyloidosis, spinal deformity, hypercalcemia, neurological disorders.

Treatment of this stage is carried out with chemotherapy, radiation, symptomatic, and immune therapy. If treatment does not help stop the tumor or achieve remission, doctors use stem cell or bone marrow transplantation. This method is quite effective and often helps in severe cases. Plasmapheresis is also performed, which helps cleanse the blood of paraproteins.

Large tumor foci are removed through surgery. Also, with the help of the operation, fragile bones are fixed and compression of blood vessels or nerve endings is eliminated.

This stage is fatal for the patient. The cause of death may be progression of the disease, sepsis, renal failure, etc.

Factors influencing survival

There are several main factors that influence survival:

Activity of the tumor process.
Stage of development.

The criteria for remission include: a decrease in plasma cells (by no less than 50%) in the bone marrow, monoclonal protein (by no less than 50%) in the urine, normalization of calcium levels, ESR, and total protein in the blood.

If it has a sluggish development, then in most cases the prognosis is favorable. There are additional factors that also affect survival.

General condition of the patient:

This factor determines how well the patient can withstand intensive therapy, which helps control the disease for a long time or complete cure. If the body has the potential to recover, then the likelihood that treatment will be effective increases significantly.

Physiotherapy:

If a person maintains and strengthens the bone apparatus, this can significantly increase the body’s resistance to the oncological process. A healthy lifestyle, proper nutrition, and giving up bad habits also have a positive effect on the immune system.

Prognosis and how long do myeloma patients live, depending on stage

The prognosis, like other cancers, depends on the stage and activity of tumor development. At the initial stage, myeloma does not have pronounced symptoms of blood cancer or bone damage, which makes diagnosing the disease much more difficult.

The percentage of 5-year survival in patients who sought medical help at the first stage of development is 50%, at the second stage – 36%, at the third stage – 10%.

If the course of chemotherapy was successful and the patient managed to achieve remission, then complete disappearance of symptoms occurs in 40% of cases, partial disappearance in 50%. But even complete remission sooner or later ends in relapse, because... the disease affects a fairly large number of tissues.

Determining the stage of myeloma is necessary to prescribe the most effective treatment plan. Fortunately, the treatment and diagnosis of myeloma are constantly improving, which improves the prognosis for survival.

In myeloma in the human body, altered plasma cells that produce immunoglobulins form tumors. The nature of the disease still remains a mystery, although the clinical signs of the disease were first described at the end of the century before last.

Causes

Scientists have identified the following factors that may contribute to the occurrence of myeloma, as well as other malignant diseases:

person’s age – most often the disease is diagnosed after 65 years of age;
exposure to ionizing radiation;
unfavorable environmental stop;
influence of toxic substances;
influence of petrochemical products;
genetics;
negative emotional situations;
infections and viruses.

The trigger for the development of myeloma is disturbances in the transformation of a certain type of lymphocyte. As a result, a colony of altered cells grows from the resulting plasma cells. These cells form tumor formations, which first affect bone tissue.

Plasmocytes displace healthy hematopoietic cells, resulting in anemia and blood clotting disorders. Since paraproteins are not able to carry out the normal protective function of the body, immunity decreases, in addition, accumulating in the blood, the total protein increases, which leads to kidney damage and urinary disorders.

Symptoms

The initial stage of the disease is often asymptomatic; this period can last for quite a long time - up to 15 years; however, an increased amount of protein can be detected in a urine test, and an increased ESR is detected in the blood.

In the future, the symptoms may become more pronounced, but they can easily be confused with signs of other diseases:

bone pain - it can appear at night or when changing body position;
anemia, which is accompanied by rapid fatigue. The skin turns pale, heart failure may develop;
a feverish state and weight loss indicate an advanced stage of the disease,
nausea and vomiting.

To differentiate myeloma from other ailments that may be accompanied by similar symptoms, it is necessary to contact specialists and fully examine the body.

As for the earliest signs of the disease, these can be a sharp decrease in physical activity, loss of appetite and rapid weight loss. Bone pain is progressive and does not go away when taking painkillers.

Myeloma patients often have various infections, and may also experience nosebleeds or increased menstrual bleeding. Characteristic changes also occur in the nervous system - in severe cases, paralysis may develop, the lower part of the body may lose sensitivity, and urinary incontinence is possible.

You should consult a doctor at the first signs of illness - pain in the bones, weakness, anemia.

Diagnostics

Diagnosis of the disease begins with asking the patient about his complaints, after which the doctor examines the patient and palpates the painful areas. Next, the following studies are prescribed:

chest x-ray or general x-ray;
bone marrow analysis;
clinical blood test;
blood test for biochemistry;
clinical urine analysis;
coagulogram;
immunoelectrophoresis;
Mancini method.

Kinds

Multiple myeloma is classified as follows:

solitary form - a single focus, which in most cases is localized in flat bones;
generalized form.

The latter is divided into:

diffuse – the bone marrow is affected;
diffuse-focal – for example, the kidneys are affected;
multiple – tumor infiltrates are found throughout the patient’s body.

Based on cell composition, myeloma is divided into:

small cell;
plasmacytic;
polymorphic cell;
plasmablastic.

In addition, myelomas can be of the following types:

Bence-Jones;
A,G,M;
diclon;
non-secreting.

According to the nature of the course, myeloma can be:

smoldering, that is, sluggish;
active;
aggressive.

Type G is most often diagnosed, less often A, Bence-Johnson myeloma is even less common.

Treatment

Treatment of the disease directly depends on the stage and form of the disease. The degree of aggressiveness of the process plays an important role. In some cases, a slow-onset disease does not require drug treatment; in this case, the doctor chooses observational tactics. Aggressive or active myelomas certainly require urgent medical intervention.

Polychemotherapy is the basis of treatment for myeloma. It is carried out using a combination of cytostatic drugs, and is carried out in courses. In addition, hormones are prescribed that eliminate the side effects of therapy and increase the effectiveness of the drugs used for treatment.

Immune therapy is no less important. With this method, periods of remission can be extended even in severe cases. Irradiation and other additional methods, such as plasmapheresis, are also used.

If such treatment is ineffective, the question arises about the need for a bone marrow and stem cell transplant. Surgeries are performed to eliminate large tumors, as well as to fix thinned bones and blood vessels. Therefore, we can say that surgery in the treatment of myeloma is an additional method of therapy.

Nutrition

The nutrition of a patient with multiple myeloma during a course of chemotherapy and during the rest period varies. When receiving chemotherapy, in most cases there is a decrease in appetite, vomiting and indigestion, so it is necessary to exclude fatty, fried and spicy foods from the diet, and do not consume canned foods, seasonings, onions and garlic.

If the white blood cell count is normal, the diet should include:

eggs, liver, fish, lean meat and poultry;
dairy products;
porridge and pasta;
baked or boiled vegetables;
fresh fruits and dried fruits;
liquid – up to 3 liters per day.

Meals should be private and in small portions.

With a reduced number of neutrophils, the following is allowed:

dairy (pasteurized) products;
well-cooked meat;
carefully cooked soups;
citrus;
boiled water, pasteurized fruits;
only packaged baked goods.

During the period of remission, nutrition should be varied, balanced and without restrictions.

Products with antitumor effects:

cereals (sprouted);
red and orange fruits;
linseed oil;
green vegetables;
cruciferous;
unrefined vegetable oils;
dried fruits;
beans, lentils;
walnuts;
seeds;
green tea.

A more precise set of permitted and prohibited foods should be discussed with your doctor; the specialist will select the optimal menu based on the stage and form of the disease, as well as based on the individual characteristics of the patient’s body and its general condition.

Life expectancy with myeloma

The main criteria on which life expectancy depends on myeloma whitening are the stage of the process and its activity. In the case of a progressive tumor, immediate therapy is necessary, which is aimed at inhibiting the proliferation of tumor cells. If no measures are taken, the disease will move from stage to stage and life expectancy will inexorably decrease.

In addition, for effective treatment, the patient’s internal organs must work without deviations, since chemotherapy destroys not only malignant cells, but also affects healthy ones, so the patient will need maximum body reserves.

In some cases, antitumor therapy does not bring results, so before prescribing chemotherapy, the doctor must make sure that the malignant cells are not resistant to the drugs. The younger the patient, the greater the likelihood that the body will withstand aggressive treatment without negative consequences. Proper nutrition, lack of stress, active lifestyle, weight control - all this also significantly affects life expectancy.

Multiple myeloma (myeloma, plasmacytoma, myelomatosis and Rustitsky-Kahler disease) is a serious disease of the hematopoietic system, which is most often diagnosed in the later stages of its course and, as a result, has a disappointing prognosis. Timely treatment can prolong the patient's life and achieve relatively long-term remission. Therefore, early diagnosis of myeloma is an important issue for all people at risk.

Characteristics of the disease

Myelomatosis is the most common disease in the group of cancers of plasma cells. The incidence of myeloma is up to 1% of all oncology cases and about 10% of blood cancer cases. Every year, 30 new cases of myeloma are diagnosed among the world's 1 million population.

With this type of oncology, a mutation occurs in one of the types of blood cells – plasma cells. Plasmocytes or plasma cells are the final form of B lymphocytes. Their function is to recognize foreign agents and produce antibodies (immunoglobulins) specific to them.

When a mutation occurs, pathological reproduction (proliferation) of one of the clones of plasma cells occurs. Altered plasma cells produce pathological immunoglobulin - a paraprotein, which is the main marker of myelomatosis in differential diagnosis.

The disease mainly affects elderly patients whose bodies are unable to tolerate severe intensive courses of chemotherapy. Therefore, the period between the appearance of the first mutated plasma cells and the diagnosis of the disease directly affects survival prognosis. At the same time, the increase in the number of pathological cells and the development of myeloma can occur extremely slowly. It can take 20-30 years from the appearance of the first plasma cells with mutations to the formation of myeloma foci.

The turning point occurs after the manifestation of clinical signs of the disease. Myeloma begins to progress rapidly. Excess paraprotein negatively affects the visceral organs (mainly the excretory system) and bones of the body.

Classification of myelomas and their diagnosis

Myelomas are classified depending on the location of altered plasma cells in healthy bone marrow tissues and the specifics of their composition. Depending on the localization of pathological cells in hematopoietic tissues, diffuse, diffuse-focal and multiple (multifocal) forms of the disease are distinguished.

The composition of the cells makes it possible to classify myelomatous tumors into plasmablastic, plasmacytic, small- and polymorphic cell. The type of atypical plasma cells is determined by tissue (histological) examination. This characteristic allows one to predict the rate of tumor growth.

One of the classifications common in medical practice also takes into account the peculiarities of the localization of the pathological focus (foci) in the skeletal system and internal organs.

Solitary or solitary myelomatous tumors are located in the bone containing bone marrow tissue or in the lymph node. Lymph nodes are directly involved in the immune response to infectious agents, and therefore are often affected by multiple myeloma.

Multiple foci of myelomatosis occupy several places at once. The bone marrow tissue of the spine, iliac and cranial bones, shoulder blades, and ribs is especially vulnerable to mutated plasma cells. Often, tumor foci form in the spleen, several lymph nodes and the central part of the tubular bones of the legs and arms.

If multiple myeloma is suspected, as well as relapse of solitary plasma cell neoplasia, a full body examination is performed using tomography.

Symptoms of myelomatosis

At an early stage, the disease can occur with virtually no symptoms. When the number of pathologically altered cells reaches a critical value, and myeloma forms a solitary or multiple focus, clinical signs of plasmacytic cancer appear.

The main symptoms of multiple myeloma:

aching pain in the bones of the limbs, shoulder blades, skull or spine;
nagging pain in the heart and joints (caused by the deposition of amyloid - a form of storage of paraproteins in the internal organs);
frequent bacterial infections;
pathological fractures of the bones of the limbs, ribs and vertebrae;
weakness, inhibition of cognitive functions, gastrointestinal disorders (caused by hypercalcemia - the release of calcium from dissolved bone tissue into the blood);
anemia;
rapid heartbeat (as a result of a compensatory mechanism in response to a lack of red blood cells);
shortness of breath, headache;
deformation of the chest due to changes in bone tissue;
nephropathy (impaired kidney function due to the formation of calcium stones in their ducts);
decreased blood clotting (with the formation of multiple bruises), often accompanied by an increase in plasma viscosity (as a result, with frequent bleeding, blood clots may form in the patient).

In every tenth patient, pathological plasma cells do not produce paraprotein. As a result, even at the stage of extensive development of myeloma, the disease is asymptomatic.

Criteria for identifying plasmacytoma at different stages of development

The intensity of symptoms and their list depend on the stage of the disease, its type (for example, in multiple myelomatosis, fractures and hypercalcemia are primarily recorded) and concomitant chronic diseases.

Signs of myeloma at different stages

Diagnostic signs	1st stage	2nd stage	3rd stage
Osteoporosis (fragility, bone destruction)	Signs of osteoporosis are absent or observed in the area of the myeloma lesion	Signs of destruction are present, but not as obvious as in stage 3 of the disease	There is intense osteoporosis
Number of bones with myelomatous lesion	Single myeloma	1-2	3 or more bones affected by tumor
Hypercalcemia		>2.55 mmol/l	>3 mmol/l
Hemoglobin level	>100 g/l	Anemia 1st or 2nd degree
Bence Jones protein concentration		from 4 to 12 g of protein in daily urine	>12 g/day
Serum paraproteins	Less than 5 g/dL (IgG) Less than 3 g/dl (IgA)	Intermediate values	More than 7 g/dl (IgG) More than 5 g/dl (IgA)

The second stage of the disease is determined more often by the exclusion method if the indicators do not meet the criteria of the 1st and 3rd. Bence Jones protein is a compound that is secreted by plasma cells. Due to its small molecular weight, it is immediately excreted by the kidneys, which makes its presence an important diagnostic sign when examining patients.

Diagnosis of the disease

To determine multiple myeloma, diagnosis must include visual, instrumental and laboratory research methods.

During the examination, the surgeon or oncologist asks the patient about complaints and the time of onset of unpleasant symptoms, measure the pulse rate, palpate the painful areas of the bones, recording whether the pain intensifies when pressed. The color of the skin is also assessed (pallor may indicate anemia), the presence of bruises and bruises, and swelling in places where the tumor is often localized. If myelomatosis is suspected, the patient is prescribed a series of tests.

The list of hardware diagnostic methods that are used to detect myelomas includes:

X-ray examination of the bones of the skeleton and chest;
Magnetic resonance imaging;
spiral computed tomography.

All three methods make it possible to identify areas of reduced bone tissue density and differentiate the pathology from other diseases of the musculoskeletal system. When affected by multiple myeloma, it is clearly noticeable on the x-ray that the bones of the skull, spine, shoulder blades and limbs are dotted with dark spots of osteolytic damage. With a solitary (single) tumor, a violation of density is observed only at the site of its localization.

Tomography is a more informative and complete method. It allows you to track bone lesions of the entire musculoskeletal system in a short time and without irradiating individual parts of the body.

Instrumental diagnostics include taking a sample (puncture) of the bone marrow to compile a myelogram. A myelogram is the result of an analysis of biomaterial (myeloid tissue), which indicates the qualitative and quantitative composition of the bone marrow.

This study makes it possible to differentiate the disease from other types of blood cancer. The main diagnostic symptom of myeloma is a pathologically increased proportion of plasma cells (more than 10-30% when the norm is up to 1.5%). In parallel with plasma cells, the content of undifferentiated blasts may increase (the norm is up to 1.1%).

Laboratory diagnostics for plasmacytoma

A key role in diagnosing myeloma is played not only by the analysis of myeloid tissue, but also by laboratory diagnostics (blood and urine samples).

The following research methods are used to diagnose myelomatosis:

general blood analysis;
Urinalysis (general and Zimnitsky);
biochemical analysis of venous blood;
coagulogram (clotting analysis);
immunoelectrophoresis;
cytogenetic analysis of plasmacytes (determination of chromosomal pathologies).

The results of a general blood test for myeloma differ significantly from the norm. The level of hemoglobin, as well as the number of platelets, leukocytes, erythrocytes, reticulocytes (precursors of red blood cells), and neutrophils decreases. The erythrocyte sedimentation rate increases (which indicates pathology without indicating its genesis) and the proportion of monocytes in the leukocyte formula. The sample may contain 1-2 plasma cells.

In a general urine test, casts, red blood cells and paraprotein light chains (Bence Jones proteins) are determined. The secreted fluid has a higher density than that of a healthy person (mainly due to pathological proteins).

Biochemical analysis shows signs of kidney damage (increased levels of uric acid, urea and creatinine) and hypercalcemia. Against the background of a small amount of albumin, due to the presence of a paraprotein, an abnormally high concentration of total protein is recorded.

Immunoelectrophoresis is performed to determine paraproteins in urine or blood plasma. Depending on the type of pathological cells, paraproteins of the IgA classes (IgD, IgE, IgG) or beta-2 microglobulins (the level of the latter indicates the stage of the disease) can be detected during the analysis.

Additional diagnostic methods include tests for the concentration of L-lactate (a marker of tissue damage), electrolytes and C-reactive protein (its concentration affects the level of myeloma growth factor - interleukin-6).

After diagnosis, an oncologist conducts an analysis to determine the prospects and rate of tumor growth (plasmacyte labeling index).

Differential diagnosis of myelomatosis

The symptoms of myelomatosis often resemble the manifestations of more common diseases of oncological and benign origin. The greatest difficulty is in differentiating the signs of plasmacytoma and benign monoclonal gammopathy.

Benign gammopathies are also characterized by the formation of clones of immunoglobulin-producing cells, but their number does not increase or occurs very slowly. The concentration of monoclonal immunoglobulins in the blood serum does not exceed 3 g/dl, and the proportion of plasma cells in the bone marrow tissue is up to 5%. Bone lesions and hypercalcemia are not recorded.

Gammopathy is the most common cause of paraproteinemia (increased amounts of abnormal protein in the blood). According to statistics, it is observed in 1-1.5% of people over 50 years of age and in 3-10% of people over 70 years of age. This condition does not require urgent treatment, but must be observed by doctors, because in 16% of cases it can develop into myeloma, and in 17% and 33% (within 10 and 20 years, respectively) into other types of hemoblastosis. In half of the cases, an increased amount of pathological protein is observed throughout the patient’s life, but does not cause his death.

Differential diagnosis with other causes of osteolytic damage (low estrogen secretion, Recklinghausen's disease, senile osteoporosis, metastases of prostate and thyroid carcinoma) is made by analyzing the concentration of paraproteins and a myelogram.

The symptoms of Waldenström's disease are also similar to the symptoms of myeloma. There are characteristic increases in monoclonal immunoglobulins (IgM), excessive production of paraproteins, and increased numbers of lymphoplasmacytic cells. The only difference is the absence of lytic bone lesions, which is determined by tomography.

Differential diagnosis of myelomatosis and other syndromes associated with paraproteinemia is also carried out in case of renal failure of unknown etiology.

Early diagnosis of myeloma is possible only with regular general clinical tests and kidney tests (blood biochemistry). If the patient takes good care of his health and annually monitors the dynamics of the results, then he has every chance to consult a doctor long before the appearance of clinical signs of myelomatosis and, with the help of intensive therapy, achieve long-term remission of the disease.

Myeloma belongs to the group of paraproteinemic hemoblastoses, in which malignant transformation of plasma cells is accompanied by their overproduction of abnormal immunoglobulin proteins. The disease is relatively rare; on average, 4 people per 100 thousand people become ill. It is believed that men and women are equally susceptible to the tumor, but, according to some data, women still get the disease more often. In addition, there are indications of a greater risk of myeloma among black populations in Africa and the United States.

The average age of patients ranges between 50 and 70 years, that is, the majority of patients are elderly people who, in addition to myeloma, have other pathologies of internal organs, which significantly worsens the prognosis and limits the use of aggressive methods of therapy.

Myeloma is a malignant tumor but it is a mistake to call it “cancer”, because it does not come from the epithelium, but from hematopoietic tissue. The tumor grows in the bone marrow, and its basis is made up of plasma cells. Normally, these cells are responsible for immunity and the formation of immunoglobulins necessary to fight various infectious agents. Plasmocytes are derived from B lymphocytes. When cell maturation is disrupted, a tumor clone appears, which gives rise to myeloma.

Under the influence of unfavorable factors in the bone marrow, there is an increased proliferation of plasmablasts and plasmacytes, which acquire the ability to synthesize abnormal proteins - paraproteins. These proteins are considered immunoglobulins, but they are not capable of performing their direct protective functions, and their increased quantity leads to thickening of the blood and damage to internal organs.

The role of various biologically active substances has been proven, in particular, interleukin-6, which is increased in patients. Bone marrow stromal cells, which perform a supporting and nutritional function (fibroblasts, macrophages), secrete interleukin-6 in large quantities, as a result of which tumor cells actively multiply, their natural death (apoptosis) is inhibited, and the tumor actively grows.

Other interleukins can activate osteoclasts, cells that destroy bone tissue, which is why bone lesions are so characteristic of myeloma. Being under the influence of interleukins, myeloma cells acquire an advantage over healthy ones, displacing them and other hematopoietic germs, leading to anemia, immunity disorders, and bleeding.

The course of the disease is conventionally divided into chronic and acute stages.

In the chronic stage, myeloma cells do not tend to multiply quickly, and the tumor does not leave the bone, patients feel satisfactory, and sometimes are not aware of the onset of tumor growth.
As myeloma progresses, additional mutations of tumor cells occur, resulting in the emergence of new groups of plasma cells capable of rapid and active division; the tumor extends beyond the bone and begins its active spread throughout the body. Damage to internal organs and inhibition of hematopoietic germs lead to severe symptoms of intoxication, anemia, immunodeficiency, which make the acute stage of the disease terminal, capable of leading to the death of the patient.

The main disorders in myeloma are bone pathology, immunodeficiency and changes associated with the synthesis of a large number of abnormal immunoglobulins. The tumor affects the pelvic bones, ribs, and spine, where tissue destruction occurs. Involvement of the kidneys can lead to chronic kidney failure, which is quite common in patients suffering from myeloma.

Causes of multiple myeloma

The exact causes of myeloma continue to be studied, and a significant role in this belongs to genetic research designed to find genes whose mutations can lead to the tumor. Thus, in some patients, activation of certain oncogenes was noted, as well as suppression of suppressor genes that normally block tumor growth.

There is evidence of the possibility of tumor growth with prolonged contact with petroleum products, benzene, asbestos, and the role of ionizing radiation is evidenced by the increased incidence of multiple myeloma among Japanese residents who suffered the atomic bombing.

Among the risk factors, scientists note:

Old age - the vast majority of patients have crossed the 70-year mark and only 1% of them are under 40 years old;
Race - the dark-skinned population of Africa suffers from myeloma almost twice as often as white-skinned people, but the cause of this phenomenon has not been established;
Family predisposition.

The identification of types and stages of a tumor reflects not only the characteristics of its growth and prognosis, but also determines the treatment regimen that the doctor will choose. Myeloma can be solitary, when one focus of tumor growth is located in the bone and there may be extramarrow neoplasia proliferations, and multiple, in which the defeat is generalized.

Multiple myeloma is capable of forming tumor foci in various bones and internal organs, and depending on the nature of its prevalence, it can be nodular, diffuse and multinodular.

The morphological and biochemical characteristics of tumor cells determine the predominant cellular composition of myeloma - plasmacytic, plasmablastic, small cell, polymorphic cell. The degree of maturity of tumor clones affects the growth rate of neoplasia and the aggressiveness of the disease.

Clinical symptoms, features of bone pathology and disorders of the protein spectrum in the blood predetermine identification of clinical stages of myeloma:

The first stage of myeloma is relatively favorable, with it, patients have the longest life expectancy provided they have a good response to treatment. This stage is characterized by: a hemoglobin level over 100 g/l, the absence of bone lesions and, as a result, a normal calcium concentration in the blood. The tumor mass is small, and the amount of paraproteins released may be insignificant.
Second stage does not have strictly defined criteria and is set when the disease cannot be attributed to the other two.
The third stage reflects tumor progression and occurs with a significant increase in calcium levels due to bone destruction, hemoglobin drops to 85 g/l and below, and the growing tumor mass produces a significant amount of tumor paraproteins.

The level of such an indicator as creatinine, reflects the degree of metabolic disorders and renal dysfunction, which affects the prognosis, therefore, in accordance with its concentration, each stage is divided into substages A and B, when the creatinine level is less than 177 mmol/l (A) or higher - stages IB, IIB, IIIB .

Manifestations of myeloma

The clinical signs of multiple myeloma are varied and fit into various syndromes - bone pathology, immune disorders, blood clotting pathology, increased blood viscosity, etc.

main syndromes in multiple myeloma

The development of a detailed picture of the disease is always preceded by asymptomatic period, which can take up to 15 years, At the same time, patients feel well, go to work and do their usual activities. Tumor growth can only be indicated by a high ESR, the unexplained appearance of protein in the urine and the so-called M-gradient in serum protein electrophoresis, indicating the presence of abnormal immunoglobulins.

As the tumor tissue grows, the disease progresses, and the first symptoms of trouble appear: weakness, fatigue, dizziness, possible weight loss and frequent respiratory tract infections, bone pain. The listed symptoms become difficult to fit into age-related changes, so the patient is referred to a specialist who can make an accurate diagnosis based on laboratory tests.

Bone damage

Bone lesion syndrome occupies a central place in the clinical picture of myeloma, since it is in these bones that neoplasia begins to grow and leads to destruction. First, the ribs, vertebrae, sternum, and pelvic bones are affected. Such changes are typical for all patients. The classic manifestation of myeloma is pain, swelling, and bone fractures.

Pain syndrome is experienced by up to 90% of patients. As the tumor grows, the pain becomes quite intense, bed rest no longer brings relief, and patients experience difficulty walking, moving their limbs, and turning. Severe, sharp pain can be a sign of a fracture, which can be caused by even a slight movement or just pressure. In the area where the tumor is growing, the bone is destroyed and becomes very fragile, the vertebrae flatten and are susceptible to compression fractures, and the patient may experience decreased height and visible tumor nodes on the skull, ribs and other bones.

bone destruction in myeloma

Against the background of bone damage by myeloma, osteoporosis (loss of bone tissue) occurs, which also contributes to pathological fractures.

Disorders in the hematopoietic system

Already at the very beginning of multiple myeloma, hematopoietic disorders associated with tumor growth in the bone marrow appear. At first, the clinical signs may be blurred, but over time, anemia becomes obvious, the symptoms of which will be pale skin, weakness, and shortness of breath. Displacement of other hematopoietic germs leads to a deficiency of platelets and neutrophils, so hemorrhagic syndrome and infectious complications are not uncommon in myeloma. A classic sign of myeloma is an acceleration of ESR, which is typical even for the asymptomatic period of the disease.

Protein pathology syndrome

Protein pathology is considered the most important characteristic of a tumor, because myeloma is capable of producing a significant amount of abnormal protein - paraproteins or Bence-Jones protein (immunoglobulin light chains). With a significant increase in the concentration of pathological protein in the blood serum, a decrease in normal protein fractions occurs. Clinical signs of this syndrome will be:

Persistent excretion of protein in the urine;
Development of amyloidosis with deposition of amyloid (a protein that appears in the body only during pathology) in internal organs and disruption of their function;
Hyperviscose syndrome is an increase in blood viscosity due to an increase in the protein content in it, which is manifested by headaches, numbness in the extremities, decreased vision, trophic changes up to gangrene, and a tendency to bleeding.

Kidney damage

Kidney damage in myeloma affects up to 80% of patients. The involvement of these organs is associated with their colonization by tumor cells, the deposition of abnormal proteins in the tubules, and the formation of calcifications during bone destruction. Such changes lead to impaired filtration of urine, hardening of the organ and the development of chronic renal failure (CRF), which often causes death in patients (“myeloma kidney”). Chronic renal failure occurs with severe intoxication, nausea and vomiting, refusal to eat, worsening anemia, and the result is uremic coma, when the body is poisoned by nitrogenous wastes.

In addition to the described syndromes, patients experience severe damage to the nervous system when the brain and its membranes are infiltrated by tumor cells; peripheral nerves are often affected, which then causes weakness, impaired skin sensitivity, pain, and even paralysis is possible when the spinal roots are compressed.

The destruction of bones and the leaching of calcium from them contribute not only to fractures, but also to hypercalcemia, when an increase in calcium in the blood leads to worsening nausea, vomiting, drowsiness, and changes in consciousness.

The growth of a tumor in the bone marrow causes an immunodeficiency state, so patients are susceptible to recurrent bronchitis, pneumonia, nephritis, and viral infections.

End-stage myeloma occurs with a rapid increase in symptoms of intoxication, worsening anemic, hemorrhagic syndromes and immunodeficiency. Patients lose weight, develop a fever, and suffer from severe infectious complications. Myeloma may progress to this stage.

Diagnosis of myeloma

Diagnosis of myeloma involves a series of laboratory tests that allow an accurate diagnosis to be made already in the first stages of the disease. Patients are given:

General and biochemical blood tests (amount of hemoglobin, creatinine, calcium, total protein and fractions, etc.);
Determination of the level of protein fractions in the blood;
Examination of urine, in which the protein content is increased, light chains of immunoglobulins (Bence-Jones protein) can be detected;
Trephine biopsy of the bone marrow in order to detect myeloma cells and assess the nature of damage to hematopoietic germs;
X-ray, CT, MRI of bones.

To correctly evaluate the research results, it is important to compare them with the clinical signs of the disease, and any one analysis will not be sufficient to diagnose myeloma.

Treatment

Treatment of myeloma is carried out by a hematologist in a hematology hospital and includes:

Cytostatic therapy.
Radiation therapy.
Prescription of alpha2-interferon.
Treatment and prevention of complications.
Bone marrow transplantation.

Multiple myeloma is considered an incurable tumor of the hematopoietic tissue, but timely therapy can make the tumor controllable. It is believed that a cure is possible only with a successful bone marrow transplant.

Chemotherapy remains the mainstay of treatment for myeloma today. allowing to prolong the life of patients up to 3.5-4 years. The successes of chemotherapy are associated with the development of a group of alkylating chemotherapy drugs (alkeran, cyclophosphamide), which have been used in combination with prednisolone since the middle of the last century. Polychemotherapy is more effective, but patient survival does not increase significantly. The development of tumor chemoresistance to these drugs leads to a malignant course of the disease, and to combat this phenomenon, fundamentally new drugs have been synthesized - apoptosis inducers, proteasome inhibitors (bortezomib) and immunomodulators.

A wait-and-see approach is acceptable in patients with stages IA and IIA of the disease without pain and the risk of bone fractures, subject to constant monitoring of blood composition, but in case of signs of tumor progression, cytostatics are mandatory.

Indications for chemotherapy are:

Hypercalcemia (increased serum calcium concentration);
Anemia;
Signs of kidney damage;
Bone involvement;
Development of hyperviscous and hemorrhagic syndromes;
Amyloidosis;
Infectious complications.

The main treatment regimen for myeloma is the combination of alkeran (melphalan) and prednisolone (M+P), which inhibit the proliferation of tumor cells and reduce the production of paraproteins. In the case of resistant tumors, as well as an initially severe malignant course of the disease, polychemotherapy is possible, when vincristine, adriablastine, and doxorubicin are additionally prescribed in accordance with the developed polychemotherapy protocols. The M+P regimen is prescribed in cycles every 4 weeks, and if signs of renal failure appear, alkeran is replaced with cyclophosphamide.

The specific program of cytostatic treatment is chosen by the doctor, based on the characteristics of the course of the disease, the condition and age of the patient, and the sensitivity of the tumor to certain drugs.

The effectiveness of the treatment is evidenced by:

Stable or increasing hemoglobin level (not lower than 90 g/l);
Serum albumin over 30 g/l;
Normal level of calcium in the blood;
No progression of bone destruction.

The use of a drug such as thalidomide, shows good results in myeloma, especially in resistant forms. Thalidomide inhibits angiogenesis (development of tumor vessels), enhances the immune response against tumor cells, and provokes the death of malignant plasma cells. The combination of thalidomide with standard cytostatic therapy regimens gives a good effect and allows, in some cases, to avoid long-term administration of chemotherapy, which is fraught with thrombosis at the site of the venous catheter. In addition to thalidomide, a drug made from shark cartilage (neovastal), which is also prescribed for multiple myeloma, can prevent angiogenesis in the tumor.

For patients under 55-60 years of age, it is considered optimal to undergo polychemotherapy followed by transplantation of their own peripheral stem cells. This approach increases the average life expectancy to five years, and complete remission is possible in 20% of patients.

Alpha2-interferon is prescribed in high doses when the patient enters a state of remission and serves as a component of maintenance therapy for several years.

Video: lecture on the treatment of multiple myeloma

Radiation therapy has no independent value in this pathology, but it is used for bone lesions with large foci of bone tissue destruction, severe pain syndrome, and solitary myeloma. The total radiation dose is usually no more than 2500-4000 Gy.

Treatment and prevention of complications include:

Bone marrow transplantation has not yet found widespread use in myeloma, since the risk of complications is still high, especially in patients over 40-50 years of age. Most often, transplantation of stem cells taken from the patient or donor is performed. The introduction of donor stem cells can even lead to a complete cure for myeloma, but this phenomenon is rare due to the high toxicity of chemotherapy, which is prescribed in the highest possible doses.

Surgical treatment of myeloma is rarely used, mainly in localized forms of the disease, when the tumor mass compresses vital organs, nerve roots, and blood vessels. Surgical treatment is possible in case of damage to the spine, aimed at eliminating compression of the spinal cord due to compression fractures of the vertebrae.

Life expectancy during chemotherapy in patients sensitive to it is up to 4 years, but resistant forms of the tumor reduce it to a year or less. The longest life expectancy is observed at stage IA - 61 months, and at stage IIIB it is no more than 15 months. With long-term chemotherapy, not only complications associated with the toxic effects of drugs are possible, but also the development of secondary tumor resistance to treatment and its transformation into acute leukemia.

In general, the prognosis is determined by the form of myeloma, its response to treatment, as well as the patient’s age and the presence of concomitant pathology, but it always serious and remains unsatisfactory in most cases. Cure is rare, and severe complications such as sepsis, bleeding, renal failure, amyloidosis and toxic damage to internal organs due to the use of cytostatics in most cases lead to a fatal outcome.

Video: myeloma in the program “Live Healthy!”

Video: doctors and patients about multiple myeloma

The author selectively answers adequate questions from readers within his competence and only within the OnkoLib.ru resource. Face-to-face consultations and assistance in organizing treatment are not provided at this time.